In the mouse, the ability to generate a Th2 T cell response is thought to represent the equivalent of an allergenic response. To evaluate this response we have compared antigen-specific IgG1 antibodies, which depend on Th2 help, vs. IgG2a antibodies, which depend instead on Th1 help. Mice were immunized with a typical allergen, purified ragweed amb A l or with a typical non-allergen, ovalbumin. Utilizing inbred mice to eliminate genetic differences, we have evaluated factors that may predispose to the allergenic response including the antigen, adjuvant, and critical cytokines such as IL-I 2 in B6 and "B6 interferon-gamma knockout" mice (IFNgamma k.o.). We have found a way to immunize B6 mice that elicits a strong Th2 response to amb Al, while eliciting little or no Th1 response. The abnormally weak Th1 response can be partially corrected by adding IL-I 2, and it largely dependent on IFNgamma production, since the IL-I 2 effect is blunted in interferon-gamma knockout mice.